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Implication of Caffeic Acid for the Prevention and Treatment of Alzheimer’s Disease: Understanding the Binding with Human Transferrin Using In Silico and In Vitro Approaches

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Abstract

In present times, a switch from chemical molecules towards natural products is taking place, and the latter is being increasingly explored in the management of diseases due to their broad range of therapeutic potential. Consumption of coffee is thought to reduce Alzheimer’s disease (AD); however, the mechanism is still unexplored. Primarily, it is thought that components of coffee are the key players in making it a neuroprotectant. Caffeic acid (CA) is found in high quantities in coffee; thus, it is being increasingly explored to decipher its neuroprotection by various mechanisms. Iron is a toxic element in a free form capable of causing oxidative damage and ultimately contributing to the pathogenesis of AD. Thus, maintaining the proper iron levels is vital and human transferrin (Htf), a glycoprotein, is a key player in this aspect. In this work, we explored the binding mechanism of CA with Htf at the atomistic level, employing molecular docking and extensive molecular dynamics simulation (MD) approaches coupled with spectroscopic techniques in a bid to decipher the mode of interaction of CA with Htf. Molecular docking results demonstrated a strong binding affinity between CA and Htf. Furthermore, MD study highlighted the Htf-CA complex’s stability and the ligand’s minimal impact on Htf’s overall structure. In silico approaches were further backed up by experimental approaches. Strong binding of CA with Htf was ascertained by UV–visible and fluorescence spectroscopy observations. Together, the study provides a comprehensive understanding of the Htf-CA interaction, adding to the knowledge of the use of CA in the treatment of AD, thereby adding another feather to its already known neuroprotective role.

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Acknowledgements

MSK acknowledges and extends their appreciation to the Researchers Supporting Project Number (RSP2023R352), King Saud University, Riyadh, Saudi Arabia, for funding this study. A.S. is grateful to Ajman University, UAE, for supporting this publication.

Funding

MSK acknowledges and extends their appreciation to the Researchers Supporting Project Number (RSP2023R352), King Saud University, Riyadh, Saudi Arabia, for funding this study.

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Authors and Affiliations

  1. Center for Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates

    Anas Shamsi & Moyad Shahwan

  2. Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates

    Moyad Shahwan

  3. College of Pharmacy, University of Michigan, 2428 Church Street, Ann Arbor, MI, 48109, USA

    Debarati Das Gupta

  4. Department of Chemistry and Biochemistry, School of Sciences, Jain University, Bengaluru, India

    K. M. Abdullah

  5. Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia

    Mohd Shahnawaz Khan

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  1. Anas Shamsi
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Anas Shamsi, Mohd Shahnawaz Khan, Debarati DasGupta, and Moyad Shahwan. The first draft of the manuscript was written by Anas Shamsi, KM Abdullah, and Debarati DasGupta. All authors read and approved the final manuscript.

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Correspondence to Anas Shamsi.

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Shamsi, A., Shahwan, M., Das Gupta, D. et al. Implication of Caffeic Acid for the Prevention and Treatment of Alzheimer’s Disease: Understanding the Binding with Human Transferrin Using In Silico and In Vitro Approaches. Mol Neurobiol 61, 2176–2185 (2024). https://doi.org/10.1007/s12035-023-03696-y

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